Molecular Playground/FIH

Factor Inhibiting HIF
Hypoxia Inducible Factor (HIF)is a transcription activator that regulates over 100 genes, many of which are important for development. HIF has been found to be over expressed in many cancers. Factor Inhibing HIF (FIH) is a non-heme Iron (II) α-ketoglutarate (α-KG) dependent asparaginyl hydroxylase that regulates HIF. In normoxic conditions (high oxygen concentrations), molecular oxygen is used to hydroxylate HIF, preventing HIF from binding to p300, a transcription co-activator. However, in hypoxic conditions (low oxygen concentrations), this hydroxylation does not occur.

FIH binds to the C-terminal Activation Domain (CTAD) of HIF. This binding domain, CTAD, (JH)is colored teal in this depiction.

Active Site
The FIH Active Site (CT)contains an Iron (II) core. The Iron core is coordinated by 2 histidine residues, an aspartate residue, an α-ketoglutarate molecule, and one water molecule. The Iron (II) is six coordinated, with α-KG chelating in a bidentate manner. In the depiction of the FIH Active Site Ligands (BH) Histidines are colored blue, Aspartate is colored red, Iron is the white sphere, and α-KG is colored yellow. The sixth coordination site is usually occupied by water, not shown here.

Enzyme Surface
In this depiction, the solvent accessible surface (JH) of FIH is shown.

Additional Resources
For additional information, see: Cancer